Moorman Jonathan, Zhang Yi, Liu Bindong, LeSage Gene, Chen Yangchao, Stuart Charles, Prayther Deborah, Yin Deling
Departments of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Biochim Biophys Acta. 2009 Aug;1793(8):1366-71. doi: 10.1016/j.bbamcr.2009.05.007. Epub 2009 May 27.
The mechanisms by which opioids affect progression of human immunodeficiency virus type 1 (HIV-1) infection are not well-defined. HIV-1 gp120 is important in the apoptotic death of uninfected, bystander T cells. In this study, we show that co-treatment of human peripheral blood mononuclear cells (PBMC) with HIV-1 gp120/morphine synergistically induces apoptosis in PBMC. Co-treatment of murine splenocytes from mu opiate receptor knockout mice with gp120/morphine resulted in decreased apoptosis when compared to splenocytes from wild type mice. Co-treatment of human PBMC or murine splenocytes with gp120/morphine led to decreased expression of beta-arrestin 2, a protein required for opioid-mediated signaling. The role of beta-arrestin 2 was confirmed in Jurkat lymphocytes, in which 1) over-expression of beta-arrestin 2 inhibited gp120/morphine-induced apoptosis and 2) RNA interference of beta-arrestin 2 expression enhanced gp120/morphine-induced apoptosis. These data suggest a novel mechanism by which HIV-1 gp120 and opioids induce lymphocyte cell death.
阿片类药物影响1型人类免疫缺陷病毒（HIV-1）感染进程的机制尚未明确。HIV-1 gp120在未感染的旁观者T细胞凋亡死亡中起重要作用。在本研究中，我们发现HIV-1 gp120与吗啡共同处理人外周血单个核细胞（PBMC）可协同诱导PBMC凋亡。与野生型小鼠的脾细胞相比，用gp120/吗啡共同处理μ阿片受体基因敲除小鼠的脾细胞，凋亡减少。用gp120/吗啡共同处理人PBMC或小鼠脾细胞会导致β抑制蛋白2表达降低，β抑制蛋白2是阿片类药物介导信号传导所需的一种蛋白质。β抑制蛋白2的作用在Jurkat淋巴细胞中得到证实，在该细胞中，1）β抑制蛋白2的过表达抑制了gp120/吗啡诱导的凋亡，2）β抑制蛋白2表达的RNA干扰增强了gp120/吗啡诱导的凋亡。这些数据提示了一种HIV-1 gp120和阿片类药物诱导淋巴细胞死亡的新机制。
